Association between measurable residual disease kinetics and outcomes of Philadelphia chromosome-positive acute lymphoblastic leukemia

Hara, Ryujiro; Onizuka, Makoto; Kikkawa, Eri; Shiraiwa, Sawako; Harada, Kaito; Aoyama, Yasuyuki; Ogiya, Daisuke; Toyosaki, Masako; Suzuki, Rikio; Machida, Sinichiro; Ohmachi, Ken; Ogawa, Yoshiaki; Kawada, Hiroshi; Matsushita, Hiromichi; Ando, Kiyoshi

doi:10.1007/s00277-021-04587-9

Cited by 2 publications

(7 citation statements)

References 21 publications

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“…The limitation of this analysis was the small number of cases; therefore, we did not evaluate the relation OS, DFS and MRD, which has the most significant impact on treatment outcomes after allo-HSCT of ALL. Previous study findings, and our results, have shown that early MRD negativity is a positive prognostic factor 9 , 15 . The importance of MRD was not demonstrated in our study cohort, which included only cases in which samples for MLPA analysis were obtained, owing to the small number of cases.…”

Section: Discussionsupporting

confidence: 81%

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Association of CDKN2A/2B deletion with relapse after hematopoietic stem cell transplantation for acute lymphoblastic leukemia

2023

BCT

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The most important prognostic factor for Philadelphia chromosome-positive acute lymphoblastic leukemia ( Ph+ ALL) is minimal residual disease (MRD). Previous studies have reported copy number variants of genes such as IKZF1 , CDKN2A/2B , and PAX5 . These gene mutations can be analyzed using multiplex ligation-dependent probe amplification (MLPA), which is less costly and easier to perform than large-scale gene mutation analyses. In this study, we performed copy number variant analysis of leukemia cells at the first onset of Ph+ALL in a case series of allogeneic hematopoietic stem cell transplantation (allo-HSCT) using the MLPA method. We analyzed how it influenced allo-HSCT prognosis together with MRD information. CDKN2A/2B copy number variations significantly increased the rate of post-transplant recurrence (P=0.025) and significantly reduced disease-free survival (P=0.015). Additionally, patients with IKZF1 deletions had a significantly higher post-transplant recurrence rate (P=0.042). Although they were positive for pre-transplant MRD, no relapse was observed in patients with wild-type copy number variations in IKZF1 or CDKN2A/2B . CDKN2A/2B copy number variation is a crucial factor that can be confirmed at initial onset as a post-transplant prognostic factor of Ph+ALL.

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Section: Discussionsupporting

confidence: 81%

“…The first MRD measurement was quantitative using real-time PCR or qualitative using nested PCR. The second measurement before transplantation was performed using nested PCR 9 . The second PCR product was confirmed using electrophoresis and defined as MRD-negative when no minor or major BCR-ABL bands were identified.…”

Section: Methodsmentioning

confidence: 99%

Association of CDKN2A/2B deletion with relapse after hematopoietic stem cell transplantation for acute lymphoblastic leukemia

2023

BCT

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“…Despite transplantation being a viable choice in most cases, one study reported an elevated incidence of relapse among MRD‐positive patients compared with those with MRD‐negative status 21 . Moreover, another study reported that the 5‐year DFS in MRD‐positive ALL patients was only 29.9% 26 . Therefore, the prognosis of MRD‐positive patients is poor.…”

Section: Discussionmentioning

confidence: 99%

“…21 Moreover, another study reported that the 5-year DFS in MRD-positive ALL patients was only 29.9%. 26 Therefore, the prognosis of MRD-positive patients is poor. Significance research efforts have focused on potential strategies to further reduce the relapse rate of ALL patients after One option is to use more intensive conditioning regimens to achieve improved efficacy in eliminating leukemia cells, 23,27,28 thereby benefiting patients to a greater extent.…”

Section: Discussionmentioning

confidence: 99%

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Intensified conditioning regimens with total marrow irradiation/etoposide/cyclophosphamide and busulfan/etoposide/cyclophosphamide overcome the impact of pre‐transplant minimal residual disease on outcomes in high‐risk acute lymphoblastic leukemia patients in complete remission

Zhao,

Xu,

et al. 2024

Cancer Medicine

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PurposeAmong high‐risk acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT), those with positive minimal residual disease (MRD) are susceptible to poor outcomes. Therefore, it is necessary to determine the most suitable preparatory regimen for these patients.MethodsData were analyzed from 141 patients who received allo‐HSCT and were diagnosed with high‐risk ALL. These patients underwent intensified conditioning regimens, including either total marrow and lymphoid irradiation (TMLI)‐etoposide (VP16)‐cyclophosphamide (CY) or busulfan (BU)‐VP16‐CY between October 2016 and November 2022. A total of 141 individuals were in complete remission (CR) before transplantation and, among all patients, 90 individuals exhibited a negative MRD status and 51 patients had a positive MRD status.ResultsIn patients who tested negative for MRD, the incidence of relapse within a 2‐year timeframe was 25.0% (24.8%–25.5%), compared with 32.2% (31.2%–33.2%) in MRD‐positive patients; however, this difference was not statistically significant. There were no significant differences in the 2‐year disease‐free survival (DFS) and 2‐year overall survival (OS) rates between the MRD‐negative and MRD‐positive groups (DFS: 67.2% (57.9%–78.1%) vs. 55.5% (42.6%–72.3%); OS: 69.0% (61.9%–88.2%) vs. 66.7% (53.9%–82.5%)). Furthermore, no notable variations were observed in the occurrence of transplant‐related mortality (TRM) and graft‐versus‐host disease (GVHD) across the two groups.ConclusionThis study reveals the benefits of TMLI‐VP16‐CY and BU‐VP16‐CY conditioning regimens in high‐risk ALL patients with CR and MRD‐positive status. A large‐scale prospective clinical trial is warranted in the future.

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Association between measurable residual disease kinetics and outcomes of Philadelphia chromosome-positive acute lymphoblastic leukemia

Cited by 2 publications

References 21 publications

Association of CDKN2A/2B deletion with relapse after hematopoietic stem cell transplantation for acute lymphoblastic leukemia

Association of CDKN2A/2B deletion with relapse after hematopoietic stem cell transplantation for acute lymphoblastic leukemia

Intensified conditioning regimens with total marrow irradiation/etoposide/cyclophosphamide and busulfan/etoposide/cyclophosphamide overcome the impact of pre‐transplant minimal residual disease on outcomes in high‐risk acute lymphoblastic leukemia patients in complete remission

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